Moss injured his ankle in the team's 27-24 victory Saturday against the Indianapolis Colts.
Buffalo's second-leading rusher behind Devin Singletary, Moss totaled 576 yards of offense and five touchdowns during his rookie season in 2020. He missed three games early in the season with a toe injury but had played in every game since. His highlight performance came during Buffalo's Week 8 victory over the New England Patriots, during which he ran for a season-high 81 yards and two touchdowns.
Moss' absence vaults 2019 third-round pick Singletary into a nearly every-down role moving forward. The Bills also have T.J. Yeldon, Taiwan Jones and undrafted rookie Antonio Williams on their roster. Williams would have to be called up from the practice squad but ran for 63 yards and two touchdowns during Buffalo's 56-26 win over Miami in Week 17.
The Bills also added veteran running back Devonta Freeman to the team's practice squad, his agent Drew Rosenhaus said Tuesday. In five games with the New York Giants, Freeman ran for 172 yards and a touchdown.
"Zack being out, we'll look at guys on our roster that we have a lot of confidence in, T.J. and Antonio and [practice squad player] Christian [Wade] there, so we'll take a look at what our options are. And like I said, we've got a lot of confidence in all three of those guys," coach Sean McDermott said Monday.
Moss started for the Bills against the Colts but was carted off the field after a run early in the fourth quarter.
While Moss was being attended to by medical trainers on the field Saturday, McDermott and Singletary stood close by. At one point, McDermott pulled the second-year back in to speak to him.
"I just told him it's his time to step up and this is what he's worked all his life for," McDermott said Monday. "And, you know, Devin's a guy that has worked extremely hard over the course of his career even before he got to the NFL. He's no stranger to hard work and he's no stranger to having to carry the load, and I know this team is 100% confident in Devin Singletary."
Per a league source, it is undecided whether Moss' injury will require surgery.